Duct Endoscopy in Assessing Cellular Atypia in the Breast Duct Fluid of Women With a Genetic Risk for Breast Cancer

OBJECTIVES: Primary * Correlate cell yield and morphology findings from ductal lavage with duct endoscopy findings and any subsequent surgical pathology findings in high-risk women with BRCA1, BRCA2, or p53 gene mutations who have cellular atypia. * Determine the prevalence of occult breast cancer in patients with cellular atypia undergoing duct endoscopy. Secondary * Determine patient acceptance of duct endoscopy. * Perform immunohistochemical analysis (including estrogen receptor, progesterone receptor, HER2-neu receptor, epidermal growth factor receptor, p53, and proliferation marker expression) for markers potentially associated with breast cancer in these patients. * Determine potential molecular markers of malignancy by gene methylation, gene expression, and proteomics in these patients. OUTLINE: Patients undergo nipple aspiration to identify productive ducts and collect fluid for tumor marker assessment followed by ductal lavage over 15 minutes. Patients undergo duct endoscopy over approximately 30 minutes under local anesthesia. If no abnormality is found, duct endoscopy is repeated in 6 months. If the repeat duct endoscopy is normal, patients continue to undergo nipple aspiration or ductal lavage as specified in protocols RMNHS-2242 and RMNHS-2269. If an abnormality is found during either the initial or repeat duct endoscopy, patients may undergo further assessment comprising imaging or biopsy and/or appropriate surgical intervention. Fluid is analyzed for tumor markers by immunohistochemistry. Candidate genes are analyzed by gene methylation studies, gene expression arrays, and proteomic analysis. Patients are followed for at least 5 years. PROJECTED ACCRUAL: A total of 45-60 patients will be accrued for this study within 2 years.